This article first appeared as the final project for PSY350 Physiological Psychology at the University of Arizona Global Campus, July 31, 2021.
Final Project: Autism Spectrum Disorder
Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects up to 2% of the general population to varying degrees of severity. People with ASD range from non-verbal and requiring intense life skill support to being mainly functional and requiring low to moderate levels of support. It is diagnosed as a lifelong persistent condition marked by deficits in social communication and interaction, and restrictive and repetitive patterns of behavior, interests, and activities (American Psychiatric Association, 2013). ASD does not have a strong consistent physical presentation, though an awkward gait and poor body-location sense are typical.
My interest in this topic stems from the diagnosis of my sons, which led me to receive my own diagnosis of ASD at a late age. As I sought definitive answers and guidance, I found that the literature, research, diagnostic criteria, and support concepts tend to leave out autistic voices: the clinical descriptions and therapies feel distinctly dehumanizing and divorced from our true experiences. This has inspired my professional goals to center around improving diagnosis, theories of etiology, support, and treatment for ASD, especially for adults who came to their self-awareness later in life. Our professional and academic understanding of ASD is evolving as we learn more about the different ways that it can manifest. More and more, treatment for comorbidities such as SUD, ADHD, depression, and anxiety are lead to identification of ASD far after the “ideal window” of early childhood. As a result, we find that current support options are scarce and that many years have often been lost to misdiagnoses such as bipolar disorder or schizophrenic orders (Fusar-Poli et al., 2020).
The term “autistic” was first coined by Paul Eugen Bleuler in 1910 to describe children who were “trapped within the self.” Though Leo Kanner and Hans Asperger were each also credited with its formal identification in 1943, historical records depict distinctly autistic behavior for far longer (Wolff, 2004). For one, Lord Henry Cavendish (b. 1731, d. 1810) was a true founder and father of modern science, being the first person to accurately measure the mass and gravitational force of the earth, among many other remarkable things. He was also incapable of intimate emotional attachment, wore the exact same outfit for his entire adult life, and flew into fits of anxiety if anyone at all engaged him directly: all distinctly autistic traits (Silberman, 2015). With ASD’s long and misunderstood history, it is no surprise that unlocking its inner biological and mechanical workings is an intense and ongoing process.
Description, Epidemiology, and Subtypes
Essential features of ASD are manifest from childhood in several domains and persist through evolved presentations into adulthood. Social interaction and communication tend to be impaired, especially in terms of reciprocation and response. Obsessive attachment to routines, repetitive behaviors, and intense anxiety as a response to deviations in patterns is common. ASD diagnosis also requires the presence of narrow and restrictive interests which produce significant anxiety responses with interrupted. Reflexive or compulsive movement called “stimming,” such as flapping hands, rocking or pacing, or percussion on self or solid objects, is another common hallmark.
ASD is identified in males over females at a rate of 4.5 to 1, at the current average, and is equally represented across national and ethnic populations. While formal diagnoses are more numerous in higher SES regions, adjusted symptomatic analysis suggests an equal representation in lower SES regions. Overall prevalence of diagnosis is currently 1 in 59 children on the average worldwide (Cardinal et al., 2020).
The DSM-V (APA, 2013) differentiates ASD into three levels of severity. Level 1, “requiring support,” represents a person who is generally poor in social situations and disinterested in social interactions, has some difficulty switching between tasks or contexts, and experiences issues with personal organization that might hamper an otherwise independent lifestyle. Level 2 “requires substantial support” with marked with deficits in verbal and nonverbal social skills, limited linguistic capacities, and inflexibility of behavior producing significant distress upon interruption. Level 3, “requiring very substantial support,” presents low-communicative or nonverbal communication in social and nonsocial settings, is unable to perform essential life skill tasks such as self-care and maintenance, and responds to interruptions of routine or interference of behavior with extreme distress.
Beyond the DSM-V debility classifications, ASD presents across a wide range of domains, styles, and personality traits, hence its “spectrum” moniker far past the taxonification of autism as “aloof,” “passive,” and “active-but-odd” as originally coined by Wing and Gould in 1979. Speech patterns can include monotone delivery, echolalia, poor volume control or concept, and vocabulary or language structure interpretations that are either extremely individual (personalized naming conventions for objects) or extremely literal and specific (narrow interpretations of words, phrases, and contexts) (Tanaka et al., 2017). Sensory processing disorders are also very common and may be the key to understanding causes and supports for behaviors. These include both over- and under-reactivity to tastes, food textures, smells, posture/body location, auditory sensitivity, auditory and language processing, photosensitivity, passive tactile discomfort, and synesthesia (DeBoth & Reynolds, 2017), among other more nuanced struggles. Social subtypes include a range of emotional priority and capacity across interactive domains such as social motivation (the desire or lack thereof to interact and affiliate with others), social communication (ability to convey accurate emotional messages verbally and non-verbally), and social recognition (ability to correctly interpret the communication intent and message of others) (Uljarević et al., 2020). As time goes on, a growing movement in professional circles seeks to formalize ASD subtypes more completely as a means of designing and providing better support in addition to honing the search for etiological and biological elements (Harris, 2019).
Etiologies, including genetics and environment
The causes of autism have been a matter of some debate in recent decades as the number of diagnoses have increased since the 1980s and 90s following its inclusion in the DSM-III, gaining nearly exponential numbers since 2000 and continuing to grow (Cardinal et al., 2020). Awareness of ASD’s existence as something far beyond mute children rocking in corners or “human computers” led to public realization of not only its prevalence but its historical existence long before Bleuler or Kramer (Silberman, 2015). This extensive (albeit anecdotal) history has indicated for etiologists studying ASD that the primary causative factors are distinctly genetic, which has been verified independently and repeatedly (Woodbury-Smith & Scherer, 2018). While the majority of research attention has been on children, the growing number of adults coming forward for diagnosis presents additional opportunities to explore the phenotype versus genotype of ASD and many of its usual comorbidities (Underwood et al., 2019) as discussed below.
As more autistic experiences are shared and investigated, the role and relevance of environmental factors are also implicated (Willfors et al., 2017; Bölte et al., 2019; Toraman et al, 2021). It has been found that those who exhibit subclinical autism behaviors in the general population share distinct genetic and biological features with those who are clinically diagnosed with ASD (Bralten et al., 2017). Thus, one might then consider that autism exists fundamentally as a genetic condition and then environmental factors influence whether it manifests merely as a personality eccentricity or as a fully defined clinical disorder (Elsabbagh, 2020). For instance, statistically, males are more likely to be diagnosed with ASD over females at around 4:1, but this may be a result of a phenotypical variation in biological gender. Alternately, a “female-protective effect” seems to prevent the manifestation of formally clinical ASD for women who carry the genetic tendency, and neuroimaging research is being conducted to determine if ASD development has gender preference or if instead the diagnostic criteria is male-skewed (Lai et al., 2017).
An interesting complication relating to gender-based etiologies, however, is the high representation of autism within transgender and gender-diverse communities (Warrier et al., 2020). Gender diversity as a possible aspect of ASD’s etiology may lie in the endocrine system, which at least would lend an explanation to the disproportionate presentation of males over females. This etiological theory suggests that impaired placental function during gestation may impact neuroendocrine and neuroimmune development through dysregulation of gonadal, thyroid, and glucocorticoid hormones. The effect may be influenced or caused by a number of environmental factors, including maternal infections, maternal hypothyroidism, birth complications, and autoimmune or hormonal imbalances (Wilson et al., 2020). The suggestion is that as male neural tissue is more sensitive to hormonal changes, especially testosterone, this potentially accounts not only for the prevalence of males but also the presence of gender-fluid and transgender ASD people (Furtunato et al., 2021).
Pathophysiology, neurotransmitters, and receptor systems
Much as with its etiology, the fundamental pathophysiological features of ASD are unknown. Theories abound, however, based on observed commonalities. One observation is that autistic patients tend to have far more neurons then neurotypical people, perhaps impairing the process of fine-tuning neurological development and specializations. Likewise, a reelin (RELN) gene mutation may interfere with appropriate neuronal migration during antenatal development, resulting in thickened cortex and smudged boundaries with white matter tracts. Other neurological pathophysiology theories include conjecture concerning impaired synaptogenesis, dendritic morphisms, excitation/inhibition imbalances in the glutamate/gamma aminobutyric acid (GABA) lifecycle, and impaired immunity causing neuroinflammation (Yenkoyan et al., 2017).
Another theory posits that gut microbiota could play an underlying role in autism, as those with ASD experience gastrointestinal symptoms at a rate four times higher than neurotypicals. The exact mechanisms are still unknown, though microbiota type imbalances, immune system abnormalities, and tryptophan metabolism alterations are all potential culprits in part or in whole (Roussin et al., 2020). Deliberate alteration of microbiota populations has been tentatively indicated to improve autistic symptoms in animal studies, though this idea is still in early development.
Multiple neurotransmitters are implicated in the presentation of ASD, including GABA, glutamate, serotonin, dopamine, N-acetyl aspartate, oxytocin/arginine-vasopressin, melatonin, vitamin D, orexin, endogenous opioids, and aceylcholine (DiCarlo et al., 2019; Garbarino et al., 2019; Brandenburg et al, 2020; Chao et al., 2020; Marotta et al., 2020). A few of these systems are more heavily implicated in ASD presentation, however. The key principle in interpretation is that the variation of symptoms in ASD can often point to the nature of neurotransmitter dysfunctions, suggesting more effective therapies.
Dopamine dysregulation and abnormalities in dopamine receptors produces executive dysfunction behaviors such as impulsivity and alternately “freezing up” at stress challenges similar to attention-deficit/hyperactivity disorder (ADHD), which is often comorbid with ASD (DiCarlo et al., 2019). The mesocorticolimbic (MCL) dopaminergic pathway that normally produces feelings of motivation and satisfaction at receiving rewards suffers reduced activation, believed in part due to a severe dysregulation of dopamine (Pavăl, 2017). Hence, ASD does not prioritize the “reward” received from social interactions in the same manner as neurotypicals might, producing a generally non-social, low-interactive feature. In a similar vein and often in the same person, some ASD-linked mutations cause malformations in the dorsal striatum (basal ganglia) resulting in a reduction of dopamine synthesis, synaptic hyperdopaminergia (excess dopamine neurotransmission), and reduced transporter function (Lee et al., 2017; DiCarlo et al., 2019; Kubota et al., 2020). This condition produces the repetitive and obsessive behaviors by over-enforcing habit formation and adding multiple “loops” to decision making, planning, and memory processing (Brandenburg et al., 2020).
Magnetic resonance spectroscopy has indicated reduced glutamate concentration in the striatum compared to non-ASD adults, leading to a scarcity of GABA which it is derived from. In children, this imbalance has been observed as lower ratios between excitatory and inhibitory mechanisms in the GABA/glutamate relationship. GABA in children is mainly excitatory and influences neuronal cell proliferation, migration, differentiation, and maturation, and scarcity during childhood influences the lifespan development trajectory of ASD, hence the insistence on early detection and treatment. For adults, the reduced availability of GABA creates the atypical sensory perceptions that are common in ASD, similar to those experienced in schizophrenia and the precursor events of epilepsy (Marotta et al., 2020).
Serotonin is another key player in ASD. Though depression is a common comorbidity, it is not neurologically consistent across the board in ASD. Clinical evidence indicates bimodal serotonergic disruption, meaning that a person with ASD could have high platelet 5-HT content (hyperserotonemia) or low platelet 5-HT count (hyposerotonemia). Hyperserotonemia, also known as serotonin syndrome, presents behaviorally as restlessness, lack of physical coordination, social irritability, and anxiety, and it is a result of increased metabolism of tryptophan into 5-HT coupled with a decreased functionality of 5-HT receptors (Garbarino et al., 2018). Relating this feature back to the microbiota connection, a 2018 study recreated the ASD hyperserotonemia events and resolved them through dietary restriction of tryptophan in animal models, indicating a possible course of therapy (Tanaka et al., 2018). On the other end of the serotonin spectrum, hyposerotonemia is marked by reduced social interaction, poor social stimuli response, and repetitive behaviors, but despite traditional protocols, selective serotonin-reuptake inhibitors (SSRIs) are often compulsively contraindicated except on a very case-by-case basis: clinical presentation for “depression” may not derive from the same neurotransmitter imbalance as it would in neurotypical people (Turner, 2020).
The primary genetic etiology of ASD is in a range of polymorphisms and mutations common also with bipolar disorder and schizophrenia (Woodbury-Smith & Scherer, 2018; Toraman et al., 2021). Numerous environmental factors have been implicated in terms of manifestation and development of ASD, including immunological influences, maternal health during pregnancy, and nutrition (Elsabbagh, 2020). Lifestyle factors are only a concern when ASD is not supported and managed. A notable comorbidity, in fact, is the capacity for developing substance abuse disorders as a means of self-medication when support and management is not available (Helverschou et al., 2019; Isenberg et al., 2021).
Perhaps more importantly than risk factors of ASD development, there is a specific profile in risk factors leading to lack of needful diagnosis. As previously mentioned, ASD’s affected demographic has traditionally been heavily skewed towards white middle- and upper-class male children due mainly to the availability of diagnostic resources in higher SES areas (Cardinal et al., 2020). Critical evaluation reveals that ASD is not ethnically or economically specific, and that lower confirmation rates in lower SES areas are painfully obvious cases of observation bias, lack of professional training, and poor distribution of diagnostic and support resources (Accordino et al., 2017). Untreated ASD can have catastrophic consequences for caregivers and individuals, not the least of which is overall poorer physical and mental health over the lifespan, reduced life expectancy (Doherty et al., 2020), and the loss of control over time from over-diagnosis and misdiagnosis (Au-Yeung et al., 2018).
Formal ASD diagnosis is ideally established between 18 and 24 months of age to optimize the opportunities for support, but diagnosis can occur at any age. The main diagnostic methods involve observational assessment, parent/caretaker interviews, self-reporting scales, or a combination of these (Chahin et al., 2020). In adults, the process can be more complicated and is often accompanied with secondary need for therapy to integrate the new diagnosis in addition to differentiating ASD from comorbidities (Fusar-Poli et al., 2020; Huang et al., 2020).
For children, a Level 1 assessment is usually performed at parents’ request if they noticed unusual behaviors or perhaps missed a developmental milestone. This step involves surveying and interviewing parents and teachers as well as collecting school records, if applicable. As an adult, a Level 1 assessment tool might be one of the qualified online surveys designed specifically for prescreening such as the Ritvo Autism Asperger’s Diagnostic Scale (RAADS-R), as the specificity and sensitivity of such tests is often questionable and therefore not sufficient for complete diagnosis higher than Level 1 (Baghdadli et al., 2017). If findings from the first stage of assessment warrant it, a Level 2 assessment is invoked. This involves scoring children on observed behavior in an objective fashion, and it helps differentiate between ASD and another possible diagnosis such as intellectual developmental disorder or a global developmental delay. One highly favored tool for children is the Rapid Interactive Test for Autism in Toddlers (RITA-T) (Lemay et al., 2020). In adults, a psychiatrist might use an interview tool such as the Schedule for Affective Disorders and Schizophrenia (SADS) or administer the Weschler Adult Intelligence Scale IV (WAIS-IV) (Groth-Marnat & Wright, 2016). A Level 3 evaluation is more interactive and helps to determine the particular features of an individual’s ASD presentation. With children, this is a personal interview with a diagnostician who leads them through a variety of more intensive evaluations and surveys. For adults, this might include personal interviews as well as administration of other assessments such as the Vineland Adaptive Behavior Scale (VABS-3).
Treatment, Therapy, and Support
With treatment starting in early childhood, therapies and medication can help manage ASD symptoms, ultimately with the goal of an independent or semi-independent lifestyle. This is not always possible, as extreme presentations often come with intellectual deficits as well, but ongoing support improves lifespan prognosis. ASD without treatment is a growing snowball of behavioral, intellectual, and social deficits. As the primary features revolve around poor communication and interpretation of social signals, untreated ASD can leave a person in deeper levels of non-communication, aggravate more violent distress responses, and suffer more profoundly from its common comorbidities.
The many common psychiatric comorbidities with ASD such as depression disorders, anxiety disorders, suicidality, ADHD, and conduct disorders, among others (Lugo-Marín et al., 2019; Hossain et al., 2020), make diagnosis a complex process, particular for adults and when illicit or off-label substance use is present. Multiple layers of assessment and accountability at every level of professional engagement are necessary to ensure the right therapies are considered, and ongoing support should be maintained as ASD tends to evolve over the lifespan, not always in a positive way. As previously mentioned, the neurochemical and pathophysiological profile of each person with ASD can vary wildly, so any program of treatment usually calls for non-drug treatments first, and later a combination of non-pharmaceutical and medication-based therapies is designed if necessary.
The most common pharmaceutical treatments for ASD are in the antipsychotic family, particularly aripiprazole, haloperidol, and risperidone (Goel et al., 2017; Alsayouf et al., 2020), though GABA therapies such as administration in simple tea have also shown promise in small trials with children (Hannat et al., 2021). Given the previously mentioned concerns regarding bimodal serotonergic dysregulation, depressive symptoms are only reluctantly treated, but when they are, first-line remedies are the SSRIs sertraline and fluoxetine, with fluvoxamine considered as a second-tier option as it produces adverse effects more frequently. Mood disorders may be treated with sodium valproate, and in the presence of tics and Tourette syndrome, clonidine may be prescribed, though aripiprazole is rapidly gaining favor as it is generally tolerated far better (Turner, 2020). When ADHD is also present – in roughly a third of adult ASD cases – excellent results have been found by treating the ADHD symptoms with bupropion, methylphenidate, or dexamphetamine both in children and adults, as addressing the ADHD features significantly mitigates the presentation of other ASD symptoms (Muit et al., 2019). On the whole, the general rule is to avoid polypharmacy in treating ASD as the underlying pathophysiologies are so disparate between individuals.
While applied behavior analysis (ABA) is often considered the go-to therapy especially for children with ASD (Irwin & Axe, 2019), the practice is falling under intense scrutiny. Its model relies on discouraging autistic behaviors such as “stimming” (self-stimulating movement), indirect communication (avoiding eye-contact), and repetition or fixation. This is considered a violation of the agency and autonomy of autistic people – child or adult – and is highly unethical, often exacerbating problem behaviors in the long term (Levinstein, 2018; Hens et al., 2019; Wilkenfeld & McCarthy, 2020). Stimming is a particularly important feature for people with ASD as it is a compulsive/reflexive behavior that enhances emotional self-regulation and re-centers attention through physical feedback; denial of stimming contributes strongly to depressive and anxiety symptoms (Kapp et al., 2019). Instead of ABA, cognitive behavior therapies (CBT) and mindfulness-based techniques that are customized to autistic people have been found to be highly effective both in children and adults for stress, anxiety, depression, and behavior regulation (Sizoo & Kuiper, 2017; Kose et al., 2018; Gaus, 2019; Wood et al., 2019; Perihan et al., 2020).
Parents and family are the traditional first-line caregivers for people with ASD, with primary care physicians (pediatricians or general practice physicians) acting as the hub for care coordination. Often, neurologists, psychiatrists, sleep specialists, and a variety of therapists (occupational, speech, physical, and mental/emotional) are organized into a plan of care that is handled by a case manager, the guardian, or the individual themselves in cases of social functionality. For the most part, people with ASD are cared for in a home environment with core family as caregivers. However, for adults unable to completely care for themselves, assisted living homes can be arranged through private and public insurance. In some cases, extreme episodes of psychotic behaviors, suicidality, and other mental or emotional disturbances can lead to psychiatric hospitalizations for short and long terms.
Suggestions for Future Research
Treatment. Developing non-pharmacological treatments that respect the agency and humanity of people with autism is a growing concern. While CBT is a highly regarded therapy, further development within this practice should focus on respecting the unique cognitive perspectives of autistics themselves at all levels of interaction rather than approaching from neurotypical positions. A major feature of this involves defining what “successful therapy” or “successful treatment” means in the context of autism. For many people with autism, they are able to present as “socially functional,” or able to “pass as neurotypical,” in a behavior colloquially termed “masking.” They are often lauded for their “success” by accomplishing such a feat, but it is both exhausting and emotionally perilous: masking feels disingenuous. With a psychology that is often heavily marked by adherence to black-and-white ethical concepts (“lying is bad,” “stealing is bad”), being forced into inauthentic modes of living is a recipe for the very worst types of depression (Kapp et al., 2019; Miller et al., 2021; Ne’eman, 2021).
Future therapeutic developments should center instead on encouraging socially and emotionally positive outcomes with specific deference to the autistic person. The idea is that people with ASD can lead productive and happy lives as autistic people, and acceptance of their traits as unique and valuable instead of stigmatized pathology will produce far more positive results for both autistic people and the general population. This extends additionally to people frequently termed “high functioning” as there is a false confluence of ASD symptom severity and intelligence: adaptive behaviors are still only adaptive, not “adoptive,” and the false dichotomy between “high-” and “low-functioning” autism often denies services and support to those who need them (Alvares et al., 2020).
Diagnostics. A major limitation and flaw of nearly all diagnostic and evaluative tools is that they were not written by or with autistics. A common complaint among socially functional adults, for instance, is that the literal and specific nature of the traditionally autistic interpretation of language often results in lower overall scores from survey tests when the questions do not apply to an individual’s experience. While this may not seem to be of great concern to many neurotypicals, for a population that thrives on specificity, even minor variations can be the difference between pursuing support or retreating into less healthy coping habits. Additionally, critical review of a number of diagnostic training programs for clinicians and other support professionals found that such programs were sorely lacking in empathy or compassion, refusing to do anything but pathologize autism (Timimi et al., 2019).
Yet another concurrent concern regarding diagnosis is the manner in which diagnostic thresholds are defined and what they mean in terms of support: does a highly intelligent person with severe sensory issues qualify for governmental disability payments, or else should they qualify instead for employment opportunities commiserate with their capabilities but sensitive to their needs? ASD as an actionable diagnosis does not neatly fit into the “abled” and “disabled” bins of modern society, further complicating the issue for many people who may earnestly need ASD support. DSM-V’s overhaul of ASD as exclusively bivariate (social and repetitive features) with four vague specifiers (intelligence, language, severity, and comorbidity) creates further aggravation by confounding heterogeneity with ambiguity, and possibly conflating multiple genotypical truths into one poorly-understood, poorly-defined, and poorly-executed insurance code (Mottron & Bzdok, 2020; Chapman & Veit, 2021). Such ambiguity indicates an overwhelming lack of understanding, and given the sheer berth of research that has done little to alleviate that short-fall, the natural answer again points to including those within the autism spectrum as authors and researchers instead of patients and subjects – to allow autistic people to humanize their existence.
Etiology. The question that comes to mind in the pursuit of etiological foundations for autism is, to what end is this question asked? Pathologizing autism to the point where it is seen as something to be avoided, cured, or trained out defies the natural order of a population that poses little to no direct harm to anyone. The quest to seek definitive etiologies can only be justified at this point if the intention is to improve treatment and support. After the hundreds of years of recorded autistic presence scientifically and anecdotally (if not longer), the current impression of autism exclusively as a burden is revealing itself as a culture-wide prejudice. Implying additionally that learning the etiology of autism could lead to preventative measures still sends a message of rejection and disapproval to those autistic people who are currently present and willing to contribute to society. So, if an etiological objective must be sought after, far more answers would likely be found by seeking the nature of a condition instead of the pathology of a disease.
Despite the steadily growing body of autism research over the last few decades, there still hangs a sense of impending discrimination in the tone and direction of much of that research. Autism that presents in so severe fashion as to be classified a disorder is legitimately concerning, but the lack of empathetic understanding of what creates a disordered presentation is distinctly missing. The empirical evidence of the special neurodiversity of autism, from neurotransmission variations to cerebral formation to sensory functionality, presents a special realization that there is a massive dimension of positive, useful, and productive experience to be explored. Inclusion – invitation – of autistic people into that exploration from this point onward is the only way to truly achieve full awareness not only of autism and neurodiversities but of the entire human neurophysiological potential.
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